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Bio Med CentralJournal of Medical Case Reports Open Access Case report The effect of voluntary fasting and dehydration on flicker-induced retinal vascular dilation in a healthy individua

Bio Med Central

Journal of Medical Case Reports

Open Access

Case report

The effect of voluntary fasting and dehydration on flicker-induced retinal vascular dilation in a healthy individual: a case report

Rebekka Heitmar, Doina Gherghel*, Richard Armstrong, Robert Cubbidge

and Sarah Hosking

Address: School of Life and Health Sciences, Aston University, Birmingham, UK

Email: Rebekka Heitmar - heitmarr@aston.ac.uk; Doina Gherghel* - D.Gherghel@aston.ac.uk; Richard Armstrong - r.a.armstrong@aston.ac.uk; Robert Cubbidge - r.p.cubbidge@aston.ac.uk; Sarah Hosking - s.l.hosking@aston.ac.uk

* Corresponding author

Abstract

Introduction: Dynamic retinal vessel analysis represents a well-established method for the

assessment of vascular reactivity during both normal conditions and after various provocations We

present a case where the subject showed abnormal retinal vessel reactivity after fasting voluntarily

for 20 hours

Case presentation: A healthy, 21-year-old man who fasted voluntarily for 20 hours exhibited

abnormal retinal vascular reactivity (dilation and constriction) after flicker provocation as measured

using the Dynamic Retinal Vessel Analyser (Imedos, Jena, Germany)

Conclusion: The abnormal vascular reactivity induced by fasting was significant; abnormal levels

of important nutrients due to fasting and dehydration could play a role through altering the

concentration of vasoactive substances such as nitric oxide This hypothesis needs further

investigation

Introduction

The assessment of retinal vessel diameters during both

normal conditions and after various provocations could

represent an important tool in investigating ocular

dis-eases as well as for the initial diagnosis and subsequent

followup of systemic disorders such as hypertension,

car-diovascular disease and diabetes [1] Since retinal vessel

size is a major determinant of vascular resistance and

hence of blood flow, any alterations in the diameter of

this vascular bed could signal perfusion-related pathology

occurring either locally or even systemically Indeed,

abnormalities of retinal vascular dynamics have been

found in both ocular [2,3] and systemic vascular diseases

Case presentation

A 21-year-old healthy man presented voluntarily for a routine research appointment involving the assessment of retinal vessel reactivity using the Dynamic Retinal Vessel Analyser (DVA) at the Aston Academy of Life Sciences, Aston University, Birmingham This device consists of a digital fundus camera combined with a CCD camera for electronic online image acquisition coupled to a video recorder for archiving [5] During a routine experiment, a chosen vessel segment of approximately 500 µm is scanned at a rate of 25 Hz After baseline measurements, flicker light is generated optoelectronically by chopping the fundus illumination at a frequency of 12.5 Hz

Published: 13 May 2008

Journal of Medical Case Reports 2008, 2:153 doi:10.1186/1752-1947-2-153

Received: 23 August 2007 Accepted: 13 May 2008 This article is available from: http://www.jmedicalcasereports.com/content/2/1/153

© 2008 Heitmar et al; licensee BioMed Central Ltd

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

(A) Initial measurement of retinal arteriole diameter under fasting and normal conditions (blue and red, respectively), (black

lines showing normal range in healthy subjects)

Figure 1

(A) Initial measurement of retinal arteriole diameter under fasting and normal conditions (blue and red, respectively), (black lines showing normal range in healthy subjects) (B) Average curve of all four observations under fasting and normal conditions

(blue and red, respectively)

Journal of Medical Case Reports 2008, 2:153 http://www.jmedicalcasereports.com/content/2/1/153

After 20 minutes of room acclimatization to obtain stabile

haemodynamic conditions, systemic blood pressure (BP)

was measured three times (1 minute apart) using a

man-ual sphygmomanometer Systolic BP (SBP) and diastolic

BP (DBP) values were obtained; the average readings for

SBP and DBP were then used to calculate the mean arterial

BP (MABP) using the formula: MABP = 2/3 × DBP+1/3 ×

SBP After instilling one drop of oxybuprocaine

hydro-chloride 0.4% in the right eye, intraocular pressure (IOP)

was also measured by means of a handheld contact

tonometer The IOP and MBP measurements were used to

calculate the mean ocular perfusion pressure (MOPP)

according to the formula: MOPP = 2/3 × MABP-IOP

After full pupil dilation was reached by using tropicamide

1.0% retinal diameters of the superior temporal retinal

artery and vein, measured approximately 1.5 disc

diame-ters away from the optic nerve head, were assessed

contin-uously over 350 seconds by using the DVA machine

according to a previously established protocol [6] Briefly,

the measurement steps were: 50 seconds of still

illumina-tion (baseline recording) followed by three cycles of 20

seconds of flicker stimulation interspersed with 80

sec-onds still illumination (representing recovery time) The

main measured outcome is the vessel width expressed in

units of measurement; for the stimulation with flicker

light, the outcome was defined as percent changed to

baseline In addition to this standard measure, the time

needed to reach maximum dilation in both the artery and

the vein during fasting and normal conditions (called the

'reaction time') was calculated

The results of the initial measurements under fasting

con-ditions and after a meal are shown in Table 1, and Figure

1A and Figure 2A As compared with what is expected in a

healthy subject under normal conditions [1,6] our results

have shown a subnormal retinal vessels response in both

the arteriole (mean dilation = 2.59 ± 1.98%) and venule

(mean dilation = 5.19 ± 2.53%) This observation has

trig-gered a more detailed history of the patient's background

and dietary habits; this later step revealed that the subject

had been voluntarily fasting for 20 hours prior to the

research appointment In order to enable us to see if this

particular aspect has had any influence on the

measure-ments, the subject was sent to have a meal and all

meas-urements were repeated immediately afterwards

The results of the second set of measurements are shown

in Table 2 The difference between the measurements

per-formed before and after the meal were statistically

signifi-cant for the retinal venous dilation (p = 0.03) but not for

the retinal artery dilation (p = 0.08)

With the subject's consent, the experiment was repeated

During these subsequent tests, the subject was in a similar physiological condition to the initial experiment Results

of all observations are shown in Table 3, and Figures 1B, 2B and 3 Retinal vein dilation and reaction time, but not artery dilation and reaction time, were statistically signifi-cantly lower in fasting versus non-fasting conditions (dila-tion: p = 0.02 and p = 0.08; reaction time: p = 0.03 and p

> 0.05, respectively) These results were comparable with the first observation that triggered the subsequent tests (a blunted vascular response during fasting and a normal response during after a meal)

Although SBP was statistically different when measured in the fasting versus non-fasting state (111.5 ± 1.17; 113.5 ± 1.17; p = 0.01) the MABP, IOP and OPP were not statisti-cally different in the fasting versus non-fasting state (p = 0.24, p = 0.11 and p = 0.64, respectively)

Discussion

This case demonstrates for the first time that despite hav-ing comparable intraocular and systemic 'pressure' condi-tions, the retinal vascular reactivity was blunted during voluntary fasting in a healthy, young individual This observation was repeatable on four separate occasions The ocular circulation has a very complex regulating sys-tem able to maintain constant blood flow and oxygen supply to the tissue despite variations in systemic BP [1,7] Autonomic nervous systems, as well as endothelial, meta-bolic, myogenic and neurogenic factors play important roles at different levels in this complex process Molecules such as nitric oxide (NO), arginine and glucose also inter-vene by regulating smooth muscle cell relaxation, and hence vascular dilation [1,8,9]

The vascular response to flickering light has been widely studied in both animals and humans [1,6] This provoca-tion results in increased metabolic demand and, there-fore, activation of NO synthase with subsequent vasodilation occurs [8,10] It is therefore possible that the abnormal vascular dilation reported here, may be the result of low NO availability; however, the mechanism resulting in NO depletion can only be hypothesized at this stage Changes in the levels of active substances such

as lactate and glucose could also play role [8,10-12] in the vascular response to flicker provocation Therefore, beside modifications in the NO dynamics, practically any change

in the quantity and composition of the circulating fluid due to dehydration and/or fasting is also capable of alter-ing vascular dynamics and BP [13] Indeed, Alghadyan et

al [14] found a significant increase in onset of retinal vein occlusion (RVO) during fasting, suggesting a possible relationship between fasting and dehydration in the pathogenesis of RVO Moreover, Lapeyraque et al

(A) Initial measurement of retinal venule diameter under fasting and normal conditions (light blue and dark blue, respectively),

(black lines showing upper and lower confidence limits in healthy subjects)

Figure 2

(A) Initial measurement of retinal venule diameter under fasting and normal conditions (light blue and dark blue, respectively), (black lines showing upper and lower confidence limits in healthy subjects) (B) Average curve of all four observations under

fasting and normal conditions (light blue and dark blue, respectively)

Journal of Medical Case Reports 2008, 2:153 http://www.jmedicalcasereports.com/content/2/1/153

Table 1: Showing retinal venule and arteriole dilation after each cycle of flickering light stimulation, as change in percentage, compared to baseline diameter as measured under fasting conditions.

CONDITION: FASTING

FLICKER STIMULATION VENOUS DILATION (in % to baseline value)

MEAN +/- STD 5.59 +/- 2.37

ARTERIAL DILATION (in % to baseline value)

MEAN +/- STD 4.63 +/- 0.63

Table 2: Showing retinal venule and arteriole dilation after each cycle of flickering light stimulation, as change in percentage, compared to baseline diameter as measured immediately after a meal.

CONDITION: AFTER MEAL

FLICKER STIMULATION VENOUS DILATION (in % to baseline value)

MEAN +/- STD 8.45 +/- 3.34

ARTERIAL DILATION (in % to baseline value)

MEAN +/- STD 9.88 +/- 1.58

Retinal venule reaction time under normal conditions (TX-V-norm) and under fasting conditions (TX-V-fast)

Figure 3

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ring during continuous peritoneal dialysis which could

result in blindness due to ocular ischaemia [15]

Although the data obtained in this case study is limited

and needs further investigation to demonstrate the exact

mechanism behind our observation, it clearly shows the

clinical significance of detailed medical history before

conducting and interpreting any test results Knowledge of

medical and/or family history and ethnic background at

the time of examination is of great importance In

addi-tion, since fluid and/or nutrient intake plays an important

role in the physiology of important variables such as BP,

vessel dynamics and blood composition, which are

com-monly used in diagnosing various systemic vascular

disor-ders, fasting and dehydration could act as confounding

factors and the clinical and/or laboratory results could be

misleading

Conclusion

We present a case of decreased retinal vascular reactivity

due to fasting and dehydration in a young and healthy

man This scenario could represent a potential case of

vasoactive substance imbalance resulting in vasodilatory

inhibition at the level of retinal vessels The importance of

this finding should be investigated in further studies and

additional tests should be included to verify our

hypothe-sis

Abbreviations

BP: blood pressure; DBP: diastolic blood pressure; DVA:

dynamic retinal vessel analyser; IOP: intraocular pressure;

MABP: mean arterial blood pressure; MOPP: mean ocular

perfusion pressure; NO: nitric oxide; RVO: retinal vein

occlusion; SBP: systolic blood pressure

Competing interests

The authors declare that they have no competing interests

Authors' contributions

RH collected the data, was involved in data analysis and

interpretation and drafting of the manuscript DG revised

the manuscript and was involved in the data analysis and

interpretation RA was involved in the statistical analysis

and interpretation RC made substantial contributions to

the design and collection SH made substantial

contribu-tions to the design and collection All authors read and

approved the final manuscript

Consent

Written informed consent was obtained from the patient for publication of this case report and any accompanying images A copy of the written consent is available for review by the Editor-in-Chief of this journal

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Table 3: Showing results of all 4 observations along with p-values, as obtained from the statistical analysis.

CONDITION: FASTING CONDITION: AFTER MEAL P-VALUE VENOUS DILATION [% change to baseline] 5.19 +/- 2.53 9.01 +/- 2.69 0.02

ARTERIAL DILATION [% change to baseline] 2.59 +/- 1.98 3.91 +/- 2.41 0.08

Publish with Bio Med Central and every scientist can read your work free of charge

"BioMed Central will be the most significant development for disseminating the results of biomedical researc h in our lifetime."

Sir Paul Nurse, Cancer Research UK Your research papers will be:

available free of charge to the entire biomedical community peer reviewed and published immediately upon acceptance cited in PubMed and archived on PubMed Central yours — you keep the copyright

Journal of Medical Case Reports 2008, 2:153 http://www.jmedicalcasereports.com/content/2/1/153

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